rs16901423

chr5-31679237-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178140.4(PDZD2):c.-361+39800T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,296 control chromosomes in the GnomAD database, including 2,714 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (2714 hom., cov: 34)
• Consequence: PDZD2 NM_178140.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

Genes affected

PDZD2 (HGNC:18486): (PDZ domain containing 2) The protein encoded by this gene contains six PDZ domains and shares sequence similarity with pro-interleukin-16 (pro-IL-16). Like pro-IL-16, the encoded protein localizes to the endoplasmic reticulum and is thought to be cleaved by a caspase to produce a secreted peptide containing two PDZ domains. In addition, this gene is upregulated in primary prostate tumors and may be involved in the early stages of prostate tumorigenesis. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZD2	NM_178140.4	c.-361+39800T>C		intron_variant		ENST00000438447.2
PDZD2	XM_005248269.5	c.-361+39800T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZD2	ENST00000438447.2	c.-361+39800T>C		intron_variant		1	NM_178140.4	P1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27990 AN: 152178 Hom.: 2712 Cov.: 34

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.00713

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.208

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.184 AC: 28012 AN: 152296 Hom.: 2714 Cov.: 34 AF XY: 0.180 AC XY: 13405 AN XY: 74480

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.00676

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.205

Alfa AF: 0.203 Hom.: 4296

Bravo AF: 0.183

Asia WGS AF: 0.131 AC: 458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.92
Dann	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16901423; hg19: chr5-31679344;